Anti–tumor necrosis factor (anti-TNF) treatment has revolutionized the management of ankylosing spondylitis (AS), but 20% to 30% of patients discontinue treatment due to failure or inadequate response to treatment. That being said, anti-TNF therapies are structurally different and have different mechanisms of action; consequently, unsuccessful treatment with 1 anti-TNF drug does not determine a patient’s potential response to another.
Anti—tumor necrosis factor (anti-TNF) treatment has revolutionized the management of ankylosing spondylitis (AS), but 20% to 30% of patients discontinue treatment due to failure or inadequate response to treatment. That being said, anti-TNF therapies are structurally different; consequently, unsuccessful treatment with 1 anti-TNF drug does not determine a patient’s potential response to another.
A review recently published in the Israel Medical Association Journal evaluated the published literature on whether treatment efficacy, once lost with a first anti-TNF treatment, could be regained in patients with AS when they switching to a second anti-TNF agent.
In order to be included within this review, a study had to have been a randomized control trial (RCT), systematic review, or observational study that evaluated anti-TNF treatment after the first anti-TNF failure, conducted from 1999 to 2016.
Danish and Norwegian registries have provided data relating to patients with AS who switched to a different anti-TNF therapy. The Danish database for biologic therapies, DANBIO, analyzed data from 432 patients who switched to a second, and 137 patients who switched to a third, anti-TNF drug. These results were compared with that of 1004 non-switched patients. In the switching groups, response and drug survival rates were found to be lower.
Among patients who switched, the effects of the first and second anti-TNF drug on disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and 50% improvement criteria (BASDAI-50) were similar during the 1-year follow-up period. However, there was a higher rate of patients achieving BASDAI-50 than reported by other investigators. The review found that 30% of patients starting anti-TNF therapy switched to a second anti-TNF drug, and noted that there is no difference in drug survival between the first, second, or third anti-TNF therapy.
In terms of immunogenicity, a chimeric monoclonal antibody, such as infliximab, encourages the production of anti-drug antibodies more intensively than humanized antibodies such as adalimumab. One study found anti-drug antibodies in 25.9% of patients, 81.8% of which were found in the patients treated with infliximab, and 18.2% in patients treated with adalimumab.
Researchers say that, because methotrexate or other immunosuppressive drugs prescribed concurrently with biologics are known to reduce the production of antibodies in patients with rheumatoid arthritis, evaluating antidrug antibody levels in patients with AS experiencing loss of efficacy may help when making drug switching decisions.
In terms of retention and predictive factors, included in this review was a large study of 1250 patients with active AS, and of the total number of patients enrolled, 1159 (92.7%) completed 12 weeks of treatment with adalimumab. At the end of the treatment period, 57.2% had achieved BASDAI 50, and 27.7% had achieved partial remission. These outcomes were strongly associated with younger age, higher C-reactive protein (CRP) levels, human leukocyte antigen B27 positivity, and anti-TNF naivete.
Furthermore, the National Swedish Biologics Registry has shown that the co-administration of conventional disease-modifying rheumatic drugs was associated with a 5-year retention of the first anti-TNF therapy in patients with a clinical diagnosis of AS or undifferentiated spondyloarthritis who started treatment with adalimumab, etanercept, or infliximab as their first anti-TNF drug between 2003 and 2010.
Overall, the results of the review found that published data primarily suggest that anti-TNF drugs are highly effective in different AS cohorts and can be associated with an increased drug retention rate. In addition, researchers suggest the consideration of positive effects of switching to another anti-TNF drug after the discontinuation of a first due to loss of efficacy over time.
Benucci M, Damiani A, Bandinelli F, et al. Ankylosing spondylitis treatment after first anti-TNF drug failure. Isr Med Assoc J. 2018;20(2):119-122. PMID:29431309.